The Influence of Probiotic Supplementation on the Severity of Anxiety and Depressive Symptoms, as Well as the Function and Composition of Gut Microbiota, Metabolic, Inflammation, and Oxidative Stress Markers in Patients With Depression

Sponsor

Medical University of Lodz (Other)

Overall Status

Recruiting

CT.gov ID

NCT05717946

Collaborator

(none)

100

Enrollment

Location

Arms

35.8

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to gather empirical evidence which will enable to evaluate the impact of probiotic supplementation on the severity of anxiety and depressive symptoms, function, and composition of gut microbiota, metabolic parameters, inflammation, and oxidative stress markers in patients with diagnosed depressive disorders.

The designed study will be prospective, randomized, placebo-controlled, and double-blind. The intervention period will last 8 weeks for each patient. The study will be conducted on 100 patients in total, who will be randomly divided into two groups, consisting of 50 patients each.

Patients included in Group I (PRO-D) will receive one capsule daily containing a probiotic mixture at a daily dose of 3×109 colony-forming units (CFU). The probiotic will be composed of two bacteria strains: Lactobacillus helveticus Rosell®-52, Bifidobacterium longum Rosell®-175, and excipients: potato starch, magnesium stearate, and the capsule shell, made of hydroxypropylmethylcellulose.

Patients included in Group II (PLC-D) will receive daily the same capsule, containing only excipients: potato starch, maltodextrin, and the capsule shell. The color, smell, and taste of the placebo will not be different from those included in the probiotic capsule.

Patients will be considered compliant if they consume >= 80% of the supplements.

The primary outcome measures will be the severity of depressive anxiety and stress symptoms assessed with Montgomery-Åsberg Depression Rating Scale (MADRS) and the Depression, Anxiety, Stress Scale (DASS) with subscales scores, the quality of life level assessed with the WHOQOL-BREF instrument. The secondary outcomes measures will include: blood pressure (BP), body mass index (BMI) and waist circumference (WC) measures, fasting glucose (fGlc), HDL cholesterol (HDL-C), triglycerides (TG), white blood cells count (WBC), neutrofiles, serum levels of C-reactive protein (CRP), the level of faecal SCFAs, faecal microbiota α-diversity and the level of oxidative stress parameters (total antioxidant capacity (TAC) and malondialdehyde (MDA)) in the blood serum.

Condition or Disease	Intervention/Treatment	Phase
Depression Anxiety	Dietary Supplement: Probiotic composed of two bacteria strains: Lactobacillus helveticus Rosell and Bifidobacterium longum Rosell. Other: control group	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, randomized, placebo-controlled, and double-blind trialProspective, randomized, placebo-controlled, and double-blind trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

double-blind trial, independent researcher is responsible for randomization and blinding.

Primary Purpose:

Treatment

Official Title:

The Influence of Probiotic Supplementation on the Severity of Anxiety and Depressive Symptoms, as Well as the Function and Composition of Gut Microbiota, Metabolic, Inflammation, and Oxidative Stress Markers in Patients With Depression

Actual Study Start Date :

Jan 4, 2021

Anticipated Primary Completion Date :

May 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group I "PRO-D" 50 patients with diagnosed depressive disorders, meeting the criteria of International Classification of Diseases (ICD-11) for 6A70-73, 6A7Y, 6A7Z, taking a probiotic composed of two bacteria strains: Lactobacillus helveticus Rosell and Bifidobacterium longum Rosell.	Dietary Supplement: Probiotic composed of two bacteria strains: Lactobacillus helveticus Rosell and Bifidobacterium longum Rosell. We plan to investigate the impact of the Lactobacillus helveticus Rosell and Bifidobacterium longum Rosell on clinical and biochemical parameters in the experimental group.
Placebo Comparator: Group II "PLC-D" 50 patients with diagnosed depressive disorders, meeting the criteria of International Classification of Diseases (ICD-11) for 6A70-73, 6A7Y, 6A7Z, taking a placebo.	Other: control group We plan to investigate the impact of a placebo on clinical and biochemical parameters in the control group.

Arm

Intervention/Treatment

Experimental: Group I "PRO-D"

50 patients with diagnosed depressive disorders, meeting the criteria of International Classification of Diseases (ICD-11) for 6A70-73, 6A7Y, 6A7Z, taking a probiotic composed of two bacteria strains: Lactobacillus helveticus Rosell and Bifidobacterium longum Rosell.

Dietary Supplement: Probiotic composed of two bacteria strains: Lactobacillus helveticus Rosell and Bifidobacterium longum Rosell.

We plan to investigate the impact of the Lactobacillus helveticus Rosell and Bifidobacterium longum Rosell on clinical and biochemical parameters in the experimental group.

Placebo Comparator: Group II "PLC-D"

50 patients with diagnosed depressive disorders, meeting the criteria of International Classification of Diseases (ICD-11) for 6A70-73, 6A7Y, 6A7Z, taking a placebo.

Other: control group

We plan to investigate the impact of a placebo on clinical and biochemical parameters in the control group.

Outcome Measures

Primary Outcome Measures

Montgomery-Åsberg Depression Rating Scale (MADRS) [8 weeks]
10-item diagnostic questionnaire used to measure the severity of depressive episodes in patients with mood disturbances. The overall score ranges from 0 to 60 (most severe depression).
Depression, Anxiety, Stress Scale (DASS21) [8 weeks]
21-item self-administered questionnaire, designed to measure the magnitude of three negative emotional states: depression, anxiety, and stress. These scores ranged from 0 ("did not apply to me at all") to 3 ("apply to me very much or most of the time").
The World Health Organization quality of life-BREF questionnaire (WHOQOL-BREF) [8 weeks]
6-item questionnaire evaluating four domains: physical health, psychological health, social relationships, and environment validated for several countries.

Secondary Outcome Measures

Blood pressure (BP) [8 weeks]
Routine measurements in a seated position after 5 minutes of rest.
Body mass index (BMI) [8 weeks]
Defined as the body mass (kg) divided by the square of the body height (m). Major adult BMI classifications are underweight (under 18.5 kg/m2), normal weight (18.5 to 24.9), overweight (25 to 29.9), and obese (30 or more).
Waist circumference (WC) [8 weeks]
Wrapping the tape measure around the widest part of stomach, across the navel.
White blood cells count (WBC) [8 weeks]
The collection will be performed under conditions of fasting, upon overnight resting, in the morning, between 8:00 and 10:00 a.m
Neutrofiles count [8 weeks]
The collection will be performed under conditions of fasting, upon overnight resting, in the morning, between 8:00 and 10:00 a.m
Serum levels of C-reactive protein (CRP) [8 weeks]
The collection will be performed under conditions of fasting, upon overnight resting, in the morning, between 8:00 and 10:00 a.m
The level of faecal short-chain fatty acids (SCFAs) [8 weeks]
Each patient included in the study will be asked to collect a sample of feces twice in a specially designed double sealed bag, which will allow keeping anaerobic conditions.
Faecal microbiota α-diversity [8 weeks]
Each patient included in the study will be asked to collect a sample of feces twice in a specially designed double sealed bag, which will allow keeping anaerobic conditions.
Total antioxidant capacity (TAC) in the blood serum [8 weeks]
The collection will be performed under conditions of fasting, upon overnight resting, in the morning, between 8:00 and 10:00 a.m
Malondialdehyde (MDA) level in the blood serum [8 weeks]
The collection will be performed under conditions of fasting, upon overnight resting, in the morning, between 8:00 and 10:00 a.m
Fasting glucose (fGlc) [8 weeks]
The collection will be performed under conditions of fasting, upon overnight resting, in the morning, between 8:00 and 10:00 a.m
HDL cholesterol (HDL-C) [8 weeks]
The collection will be performed under conditions of fasting, upon overnight resting, in the morning, between 8:00 and 10:00 a.m
Triglycerides (TG) [8 weeks]
The collection will be performed under conditions of fasting, upon overnight resting, in the morning, between 8:00 and 10:00 a.m

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Depressive disorders diagnosed according to ICD-11,
Age between 18 - 70 years,
MADRS score >=13,
Antidepressant and antianxiety medications not changed 3 weeks prior to the recruitment visit.

Exclusion Criteria:

Pregnancy,
An infection/vaccination and/or treatment with antibiotics in the previous 4 weeks,
Supplementation with pro- or prebiotics in the previous 4 weeks,
Having a diagnosis of autoimmune, serious immunocompromised, inflammatory bowel diseases, cancer, IgE-dependent allergy, or severe kidney failure in the previous 4 weeks,
body mass index (BMI)> 35,
glomerular filtration rate (GFR)< 30 ml/min/1,72 m2,
unstable thyroid dysfunction (TSH < 0,27 or > 4,2 μIU/ml) in the previous 4 weeks,
Psychiatric comorbidities (except specific personality disorder, additional specific anxiety disorder, and caffeine, and nicotine addiction),
Regular treatment (more than 3 days a week) with PPIs, metformin, laxatives, systemic steroids, or NSAIDs in the previous 4 weeks,
Significant change in dietary pattern in the previous 4 weeks,
Significant change in daily physical activity or extreme sports activity in the previous 4 weeks,
Significant change in dietary supplementation in the previous 4 weeks,
Significant change in smoking pattern in the previous 4 weeks,
High risk of suicide,
Is participating in, or has recently participated in, another research study involving an intervention that may alter outcomes of interest to this study,
Any other condition or situation which, in the view of investigators, would affect the compliance or safety of the individual taking part.